Citations 2
frontMIND: Phase 3 study of tafasitamab (Tafa) plus lenalidomide (Len) and R-CHOP for patients (pts) with newly diagnosed diffuse large B-cell lymphoma (DLBCL).
Lenz, Georg, Trněný, Marek, Burke, John M., Nowakowski, Grzegorz S., Düll, Johannes, Jeon, Youngwoo , Cheah, Chan, Westin, Jason, Ye, Joseph Z., Caguioa, Priscilla B. , Belada, David, Shin, Ho Jin, Amorim, Sandy, Colucci, Philomena, Ioannidis, Sonia, Lenz, Georg , Trněný, Marek , Burke, John M. , Nowakowski, Grzegorz S. , Fox, Christopher P. , Chiappella, Annalisa , Westin, Jason R. , Belada, David , Oh, Sung Yong , Colucci, Philomena M., Cheng, Lulu L , Vitolo, Umberto
Journal of Clinical Oncology | June 3, 2026 | Volume: 44 | Issue: 17_suppl | Pages: No page available
10.1200/jco.2026.44.17_suppl.lba7000
LBA7000 Background: ~40% of DLBCL pts are not cured with first-line (1L) R-CHOP, underscoring a significant unmet need for more effective 1L regimens. Tafa (anti-CD19 mAb) + Len-R-CHOP in the phase 1b First-MIND study demonstrated safety and efficacy in pts with newly diagnosed disease. frontMIND, a phase 3, double-blind, placebo-controlled study, compared Tafa-Len-R-CHOP vs R-CHOP in pts with high-risk aggressive BCLs. Methods: Pts aged 18–80 y with newly diagnosed, high-intermediate/high-risk DLBCL or HGBL (IPI 3–5, aaIPI 2–3 if ≤60 y) and ECOG PS 0–2 were randomized 1:1 to Tafa-Len-R-CHOP or R-CHOP. Primary endpoint was investigator-assessed PFS; secondary endpoints included: EFS, OS, CR, ORR, safety. Results: At primary analysis (data cutoff Oct 20, 2025), 899 pts were randomized to Tafa-Len-R-CHOP (n=448) or R-CHOP (n=451); baseline characteristics were similar between arms. With a median follow-up of 35.2 mo, Tafa-Len-R-CHOP achieved a statistically significant improvement in PFS vs R-CHOP (HR 0.75 [95% CI: 0.59, 0.96]; P =0.019) in the overall population; in pts with centrally confirmed lymphoma subtypes (n=773), PFS HR was 0.68 (95% CI: 0.52, 0.88) and 24-mo PFS was 72.7% vs 62.2%. PFS benefit was observed with Tafa-Len-R-CHOP in both molecular COO subtypes, ABC and GCB (data will be presented). Tafa-Len-R-CHOP significantly improved EFS vs R-CHOP; CR and ORR were similar between arms and HR for OS was 0.85 (final OS planned at 5y) (Table). Any-grade TEAEs were similar in treatment arms (98.6% vs 97.1%); more grade ≥3 TEAEs occurred with Tafa-Len-R-CHOP vs R-CHOP (86.7% vs 76.1%). Discontinuations due to TEAEs occurred in 25.7% vs 17.9% and deaths due to TEAEs in 5.9% vs 3.8% of pts for Tafa-Len-R-CHOP vs R-CHOP. Overall, there were fewer deaths with Tafa-Len-R-CHOP vs R-CHOP (18.5% vs 21.7%). Conclusions: The primary endpoint of frontMIND was met; Tafa-Len-R-CHOP resulted in a significant 25% reduction in risk of disease progression or death compared with R-CHOP, with an 8.2% difference in 24-month PFS rate in the overall population and 10.5% difference in pts with centrally confirmed lymphoma subtypes. TEAEs were manageable and consistent with the expected safety profile. Tafa-Len-R-CHOP represents a potential new 1L standard of care for pts with both COO subtypes of high-risk DLBCL or HGBL. Clinical trial information: NCT04824092 . Efficacy outcomes by treatment arm.* Variable Tafa-Len-R-CHOP(n=448) R-CHOP(n=451) HR or OR(95% CI) P value PFS, # events (%) † 121 (27.0) 155 (34.4) 0.75 (0.59, 0.96) 0.019 PFS rate at 24 mo, % 71.1 62.9 − − PFS rate at 36 mo, % 67.3 60.7 − − EFS, # events (%) 154 (34.4) 191 (42.4) 0.79 (0.64, 0.97) 0.026 OS, # events (%) 82 (18.3) 95 (21.1) 0.85 (0.63, 1.14) 0.270 CR at EOT, n (%) 292 (65.2) 294 (65.2) 0.998 (0.76, 1.31) 0.987 ‡ ORR at EOT, n (%) 360 (80.4) 343 (76.1) 1.290 (0.94, 1.78) 0.120 ‡ *Investigator-assessed. † Progressive disease or death from any cause. ‡ Nominal P value.
Acalabrutinib Plus Bendamustine-Rituximab in Untreated Mantle Cell Lymphoma
Wang, Michael , Song, Yuqin, Jurczak, Wojciech, Kahl, Brad S. , Chu, Michael P., Kryachok, Iryna, Fogliatto, Laura, Cheah, Chan Y. , Morawska, Marta , Li, Yufu, Patti, Caterina , Forsyth, Cecily , Lesley, Robin, Ramadan, Safaa, Rule, Simon, Dreyling, Martin , investigators, for the ECHO, Cazap, Nicolás, Foncuberta, María Cecilia, Garate, Gonzalo, Gustavo, Jarchum, Pavlovsky, Miguel Arturo , Riveros, Dardo, Baker, Ross, Butler, Jason, Cannell, Paul , Cheah, Chan, Forsyth, Cecily, Giri, Pratyush, Johnston, Amanda, Lee, Denise , Lee, Hui‐Peng, Mapp, Sally, Roncolato, Fernando , Thant, Aung , Walker, Patricia, Doo, Nicole Wong, Demuynck, Hilde, Offner, Fritz , Hende, Vanessa Van, Vergote, Vibeke, Wu, Ka Lung , Chiattone, Carlos, Azevedo, Sergio de, Fogliatto, Laura, Fonseca, Ana, Hamerschlak, Nelson, Lazaretti, Nicolas, Rocha, Vanderson, Salvino, Marco, Santucci, Rodrigo, Schaan, Mariza, Scheliga, Adriana, Vieira, Garles Miller, Berinstein, Neil, Boutin, Mélina , Chu, Michael, Keating, Mary‐Margaret, Schattner, Ariah, Restrepo, Diego Villa, Cen, Xinan, Du, Xin, Feng, Ru, Gao, Sujun, Huang, Haiwen, Ji, Jie, Jin, Jie, Ke, Xiaoyan, Li, Dengju, Li, Fei, Li, Jianyong, Li, Junmin, Li, Yan, Li, Yufu, Li, Zhenyu, Lin, Li'e, Liu, Tingbo, Lv, Fangfang , Shuang, Yuerong, Sun, Lan, Sun, Xiuhua, Wang, Zhao, Wu, Huijing, Xi, Yaming, Xia, Ruixiang, Xue, Hongwei, Yang, Haiyan, Yi, Shuhua, Zhang, Cheng, Zhang, Huilai, Zhang, Mingzhi, Zhang, Qingyuan, Zhao, Xielan, Zhou, Hui, Hajek, Roman, Jindra, Pavel , Mayer, Jiri, Novak, Jan, Abraham, Julie, Bijou, Fontanet, Bouabdallah, Kamal , Cymbalista, Florence, Guilbert, Sophie, Laribi, Kamel, Rodon, Philippe, Decker, Thomas, Dreger, Peter, Dreyling, Martin, Hess, Georg, Lenz, Georg, Stilgenbauer, Stephan, Tummes, Dirk, Anargyrou, Konstantinos , Dimopoulos, Meletios-Athanassios, Kapsali, Eleni, Kyriakou, Despoina, Panayiotidis, Panayiotis, Pappa, Vasiliki , Stavroyianni, Niki, Cheng, Hoi Ching, Kwong, Yok-Lam, Lee, Harold, Ng, Ting Ying, Wong, Raymond, Borbényi, Zita , Illés, Árpád, Lázár, Zsolt, Nagy, Ãgnes , Nagy, Zsolt, Schneider, Tamas, Avivi, Irit, Gurion, Ronit, Horowitz, Netanel, Ronson, Aaron, Arcaini, Luca, Boccomini, Carola, Ghia, Paolo, Luminari, Stefano, Plenteda, Caterina, Santoro, Armando, Zilioli, Vittorio Ruggero, Zinzani, Pier Luigi, Choi, Ilseung , Ennishi, Daisuke , Ichikawa, Satoshi, Ishikawa, Takayuki, Izutsu, Koji, Kato, Koji, Maruyama, Dai, Nagai, Hirokazu, Ota, Shuichi, Saito, Toko, Sakai, Rika, Suzuki, Ritsuro, Uoshima, Nobuhiko , Yano, Takahiro, Yoshida, Isao, Eom, Ki-Seong, Kim, Jin Seok, Kim, Seok Jin, Lee, Jung-Hee, Mun, Yeung Chul, Yoon, Sung Soo , Arreguin, Elsa Veronica Avila, Andrade, Adriana Dominguez, Almaguer, David Gómez, Vera, Maria Silvia Rivas, Anaya, Luis Solís, Berkahn, Leanne, Pemberton, Lucy, Simpson, David, Beltrán, Brady, Quintana, Shirely, Revilla, Jose Carlos, Vargas, Ernesto, Grosicki, Sebastian , Hałka, Janusz , Jedrzejczak, Wieslaw, Knopińska-Posłuszny, Wanda, Krzanowski, Jacek, Lech-Maranda, Ewa, Robak, Tadeusz, Rzepecki, Piotr , Wróbel, Tomasz, Borsaru, Gabriela, Ciuleanu, Tudor Eliade, Danaı̈la, Catalin, Lazaroiu, Mihaela, Alexeeva, Julia, Chistyakov, Valeriy, Manikhas, Georgy, Mikhailova, Natalia, Proydakov, Andrey, Volodicheva, Elena , Voloshin, Sergey, Bastos, Mariana, Cordoba, Raul, Codina, José , Gonzalez, Eva Maria, Marin, Ana, Panizo, Carlos, Rodriguez, Guillermo, Salar, Antonio, Sancho, Juan-Manuel, Velo, Jose A, Chiu, Chang-Fang, Hsiao, Liang-Tsai, Kuo, Ching-Yuan, Lin, Tung-Liang, Lysa, Tamila, Maslyak, Zvenyslava, Nogaieva, Larysa, Polenkov, Sergey, Usenko, Ganna, Agajanian, Richie, Anz, Bertrand, Chaudhry, Arvind, Chiu, Alden , Cultrera, Jennifer, D’Olimpio, James, Dunleavy, Kieron, Fanning, Suzanne, Flinn, Ian, Gabrail, Nashat, Gallinson, David, Goldenberg, Alec, Graf, Solomon, Grover, N., Hess, Brian, Hoffman, Marc, Isufi, Iris, Kahl, Brad, Kambhampati, Suman , Kirkel, Dean, Diaz, Guillermo Lazo, Levy, Moshe, Liu, Delong, Mead, Monica , Paludo, Jonas, Patel, Anjan, Peles, Shachar, Persky, Daniel, Portell, Craig, Rosenthal, Allison, Sano, Dahlia , Smith, Sonali , Smith, Stephen, Spurgeon, Stephen, Tache, Jason, Tsai, Michaela, Veltri, Lauren, Wang, Michael, Yimer, Habte, Bach, Quoc Khanh, Đỗ, Huyền Nga, Luu, Hung Vu, Khoa, Trọng, Phạm, Như Hiệp, Panizo, Carlos , Kriachok, Iryna , Kahl, Brad S , Paludo, Jonas , Cheah, Chan Yoon , Morawska, Marta , Sancho, Juan-Manuel , Forsyth, Cecily , Dreyling, Martin , Belada, David , Song, Yuqin , Paludo, Jonas , Fogliatto, Laura , Zhang, Jingyang , Lesley, Robin, Ramadan, Safaa Mahmoud , Garate, Gonzalo, Riveros, Dardo Alberto, Cannell, Paul , Cochrane, Tara , Giri, Pratyush, Mapp, Sally , Doo, Nicole Wong , Demuynck, H, Hende, Vanessa Van, Vergote, Vibeke K. J. , CHIATTONE, CARLOS SÉRGIO , Farias, João Samuel de Holanda , Fonseca, Ana Rita Da , Rocha, Vanderson , Oliveira, José Salvador Rodrigues de , Scheinberg, Phillip , Scheliga, Adriana , Vieira, Garles Miller Matias , Berinstein, Neil Lorne , Shuang, Yuerong , Hájek, Roman , Mayer, Jiřı́ , Bijou, Fontanet , Cymbalista, Florence, Delwail, Vincent , Genet, Philippe , Dreger, Peter , Heß, Georg , Lenz, Georg , Stilgenbauer, Stephan , Kapsali, Eleni , Katodritou, Eirini , Kyriakou, Despoina S, Panayiotidis, Panayiotis G. , Symeonidis, Argiris , Schneider, Tamas J., Avivi, Irit, Gurion, Ronit , Horowitz, Netanel A. , Arcaini, Luca , Boccomini, Carola , Luminari, Stefano , Santoro, Armando, Zilioli, Vittorio Ruggero , Zinzani, Pier Luigi , Fukushima, Kentaro , Izutsu, Koji , Maruyama, Dai , Tatetsu, Hiro , Kim, Sang‐A , Oh, Sung Yong , Arreguin, Elsa Ávila, Gómez‐Almaguer, David , Issa, Samar , Revilla, Jose C., Vargas, Ernesto, Lech-Maranda, Ewa, Robak, Tadeusz , Borsaru, Gabriela, Ciuleanu, Tudor–Eliade , Danaila, Catalin-Doru , Alexeeva, Julia, Briones, Javier , Salar, Antonio , Yuste, Victor Jimenez, Chen, Chien‐Yuan , Kuo, Ching‐Yuan, Anz, Bertrand, Cultrera, Jennifer L. , D’Olimpio, James, Dunleavy, Kieron , Gabrail, Nashat , Gallinson, David, Goldenberg, Alec S., Goy, Andre Henri , Graf, Solomon A. , Hess, Brian, Kirkel, Dean, Portell, Craig A. , Rosenthal, Allison , Stevens, Don, Veltri, Lauren Westfall , Yimer, Habte, Tran, Thanh Tung
Journal of Clinical Oncology | May 1, 2025 | Volume: 43 | Issue: 20 | Pages: 2276-2284
PURPOSE The combination of the Bruton tyrosine kinase inhibitor ibrutinib with bendamustine-rituximab for first-line treatment of mantle cell lymphoma (MCL) prolonged progression-free survival (PFS), but without improvement in overall survival (OS), likely because of toxicity. Acalabrutinib was shown to be efficacious and less toxic than ibrutinib in a head-to-head trial in chronic lymphocytic leukemia and therefore might lead to better outcomes in MCL. METHODS Patients 65 years and older with previously untreated MCL received acalabrutinib (100 mg twice daily) or placebo (until disease progression or unacceptable toxicity), plus six cycles of bendamustine (90 mg/m 2 once daily; days 1 and 2) and rituximab (375 mg/m 2 as a single dose; day 1) followed by rituximab maintenance in responding patients for 2 years. Crossover to acalabrutinib at disease progression was permitted. The primary end point was PFS per the independent review committee; overall response rate and OS were secondary end points. RESULTS In total, 598 patients were randomly assigned, with 299 in each arm. At a median follow-up of 49.8 months using the reverse Kaplan-Meier method, the median PFS was 66.4 months in the acalabrutinib arm and 49.6 months in the placebo arm (hazard ratio [HR], 0.73 [95% CI, 0.57 to 0.94]; P = .0160). Benefit was seen across all subgroups, including those with high-risk features. Overall response/complete response rates were 91.0%/66.6% and 88.0%/53.5% in the acalabrutinib and placebo arms, respectively. OS was not significantly different (HR, 0.86 [95% CI, 0.65 to 1.13]; P = .27). Grade 3 or greater adverse events were reported in 88.9% and 88.2% in the acalabrutinib and placebo arms, respectively. CONCLUSION The combination of acalabrutinib with bendamustine-rituximab significantly improved PFS. Clinical benefit of acalabrutinib with bendamustine-rituximab was achieved with manageable toxicity.